Trans-sialidases can transfer sialic acids, preferably alpha-2,3-bonded sialic acids, from a donor molecule to an acceptor molecule, whereby again, alpha-2,3-glycosidic bonds can be formed, preferably on a β-terminal galactose residue.
The term sialic acids includes all N and O derivatives of neuraminic acid (Blix et al, 1957). Neuraminic acid (5-amino-3,5-didesoxy-D-glycero-D-galacto-nonulo-pyranosonic acid) is an amino sugar with a backbone consisting of nine carbon atoms, which acquires a very acid pK value of 2,2 due to the carboxyl group on the C atom 2, and so is negatively charged under physiological conditions.
The non-substituted form is very unstable and does not occur in nature in free form (Schauer, 1982). However, more than 40 natural derivatives of neuraminic acid are meanwhile known (Schauer and Kamerling, 1997). The two sialic acids which most frequently occur in nature are the N-acetylneuraminic acid (Neu5Ac), the forerunner of all glycosidically bonded sialic acids (Schauer, 1991) and the N-glycolylneuraminic acid (Neu5Gc) which emerges by means of hydroxylation of the methyl group of the N-acetyl residue of CMP-Neu5Ac (Shaw and Schauer, 1988). The hydroxyl groups of these two sialic acids can be substituted by acetyl, lactyl, methyl, sulphate and phosphate residues in different combinations, and this leads to the great structural variety of the sialic acids (Schauer, 1991; Schauer and Kamerling, 1997).
The greatest number of the naturally occurring sialic acids are bonded as a component part of oligosaccharides, polysaccharides and in particular glycoconjugates (Schauer, 1982). However, polysialic acids are also known from transgenic microbe production. Sialated glycoconjugates mainly occur in the outer membrane of cells, but are however important components of the serum of mucosa (Traving and Schauer, 1998). The sialic acids protect glycoproteins and cells from attack by proteases and other enzymes, and so from decomposition (Reuter et al., 1988). The mucosa of the gastrointestinal tract which contain sialic acid not only form effective protection from the digestion enzymes, but also protect the tissues lying among these from the penetration of pathogenic bacteria (Kalm and Schauer, 1997).
Sialic acids fulfil a very important function with molecular and cellular identification processes. Here, they conceal receptors and so prevent interactions between receptors and ligands (Schauer, 1985; Kelm and Schauer, 1997). Sialic acids therefore protect eg. serum glycoproteins and erythrocytes against decomposition and phagocytosis whereby they conceal galactose residues present here. If the terminal sialic acids are separated, the subterminal galactose residues can be bonded by lectins on hepatocytes or phagocytes, and the result is endocytosis of the serum proteins or erythrocytes. A further example is the protection of the body's own tissues, but also of many highly sialated tumours before identification by the immune system (Pilatte et al., 1993). If the protective sialic acid layer is lost, autoimmune reactions can occur.
Sialic acids also serve as identification points for the body's own cells and hormones, and so play an important role in cellular interactions (Kelm and Schauer, 1997). With inflammation, endothel cells express selectins on their surface which identify certain sialated structures (eg. sialyl Lewis X) on leucocytes so that the same bind to the endothel cells and can penetrate into the tissue (Lasky, 1995). Furthermore, the activation of the T-cells of the humoral immune defence is influenced by the effect of trans-sialidases (Gao et al., 2001). Sialoadhesins (siglecs) such as the myelin-associated glycoprotein (MAG) also bind highly specifically onto sialated glycans (Kelm et al., 1996; Crocker et al., 1998). In the nervous system, the myelin-associated glycoprotein is involved, among other things, in the myelinisation and in the regulation of axonal growth. It is therefore not astonishing that it was recently discovered that trans-sialidases are involved by the transfer of sialic acids in the differentiation of nerve cells and glia cells (Chuenkova et al., 2001). CD-22 is another sialic acid-binding receptor which occurs on lymphocytes and makes possible the “dialogue” of T- and B-lymphocytes. The siglecs family consists on average of more than 10 molecular-biologically characterised representatives.
Sialic acids are however not only important with the body's own identification processes, but are also receptors for certain bacteria, viruses and toxins. For example, the binding of the tetanus toxin to gangliosides of nerve synapses happens by means of sialic acids (Schauer et al., 1995). The sialic acid-specific adhesion by means of microbial lectins (Sharon and Lis, 1997) is often a critical step with infectious diseases, for example with newborn meningitis brought about by some E. coil stems or with infections of the gastric mucosa by means of Helicobacter pylori. Above all, the flu viruses Influenza A and B viruses attach onto the cells to be infected by means of sialic acid (Schauer, 2000).
Modifications of the sialic acids, in particular the O-acetylation, are of great significance in the regulation of molecular and cellular identification (Schauer, 1991). Influenza C viruses thus bind specifically to 9-O-acetylated sialic acids on bronchial epithels (Herrier et al., 1985), whereas the O-acetylation prevents binding of the influenza A and B viruses (Higa et al., 1985). Above all, however, the O-acetylation of sialic acids is very important for the morphogenesis and development of different tissues (Varki et al., 1991). With neuroectodermal tumours it is increased (Hubi et al., 2000; Fahr and Schauer, 2001), and with cancer of the colon it is decreased (Corfield et al., 1999). Sialic acids are essential modulators of the biological behaviour of tumours (Schauer, 2000).